Addressing infectious disease in a therapeutically relevant fashion requires an understanding of both the microbial virulence factors that contribute to the disease process and the manner in which these factors impact the host immunological and inflammatory response. Achieving this will provide an opportunity to develop novel strategies to influence the pathogen and/or host response in favor of the host, thereby providing a perfect opportunity for clinically relevant translational research. Thus, achieving this understanding continues to be the overall goal of our Center for Microbial Pathogenesis and Host Inflammatory Responses. The key element to accomplishing this is to assemble a critical mass of investigators, each under the mentorship of established senior faculty, whose research is consistent with this underlying scientific theme and the overall goals of our Center. The underlying hypothesis that ties these investigators together is that targeting diverse microbial pathogens in the context of their impact on immunological and inflammatory responses in their common human host will optimize opportunities for the elucidation of common themes with respect to the host response and its adverse consequences on the disease process. To this end, this application brings together as Project Leaders four investigators who focus on diverse microbial pathogens from the point of view of both the pathogens themselves and their impact on host inflammatory responses. To support these investigators, and to build a pipeline of new investigators whose research is consistent with our underlying scientific theme, we propose to provide an integrated and highly interactive faculty development plan for all Center investigators that leverages the resources developed during Phase I to enable our Phase II Project Leaders and other Center investigators to establish independently-funded research careers in an area consistent with this underlying theme (Aim 1); to utilize the Administrative and Scientific Development (Core A) and Research and Technical Advancement (Core B) cores developed during Phase I to continue to promote the scientific development of Center investigators and enhance the overall research infrastructure on the host campuses (Aim 2); and to build on the success of our Phase I efforts to recruit additional investigators whose research is consistent with the underlying scientific theme and promote the development of collaborative, synergistic research relationships among Center investigators (Aim 3). This will allow us to build on the success of Phase I Project Leaders to establish a self-sustaining Center for Microbial Pathogenesis and Host Inflammatory Responses.